This has been recognized in the settings of certain cancers (such as myeloid leukemia), lung infections, or environmental exposure to dusts or chemicals, such as nickel.

[4] Although the cause of PAP was not originally understood, a major breakthrough in the understanding of the cause of the disease came by the chance observation that mice bred for experimental study to lack a hematologic growth factor known as granulocyte-macrophage colony stimulating factor (GM-CSF) developed a pulmonary syndrome of abnormal surfactant accumulation resembling human PAP.

[6] Familial or sporadic inactivating mutations in one of the two parental GATA2 genes produces an autosomal dominant disorder termed GATA2 deficiency.

The GATA2 gene produces the GATA2 transcription factor which is critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissue-forming cells.

GATA2 mutation-based pulmonary alveolar proteinosis is associated with normal levels of GM-CSF and commonly improves or is avoided in afflicted individuals who successfully receive a hematopoietic stem cell transplantation.

[14] Electron microscopy of the sample, although not typically performed due to impracticality, shows lamellated bodies representing surfactant.

Other treatments still being studied include subcutaneous and inhaled GM-CSF, and rituximab, an intravenous infusion that works to stop the production of the autoantibodies responsible for autoimmune PAP.

[citation needed] In a recent epidemiologic study from Japan,[26] Autoimmune PAP has an incidence and prevalence higher than previously reported and is not strongly linked to smoking, occupational exposure, or other illnesses.

[29] In their case series published in the New England Journal of Medicine on June 7 of that year, they described 27 patients with pathologic evidence of periodic acid Schiff positive material filling the alveoli.

[citation needed] The reported treatment of PAP using therapeutic bronchoalveolar lavage was in 1960 by Dr. Jose Ramirez-Rivera at the Veterans' Administration Hospital in Baltimore,[30] who described repeated "segmental flooding" as a means of physically removing the accumulated alveolar material.